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000295900 1001_ $$aSander, Pascal$$b0
000295900 245__ $$aDesign, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example.
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000295900 500__ $$a 2025, 68, 1, 674–694
000295900 520__ $$aThe human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer. In a target hopping example we started with the focal adhesion kinase (FAK) inhibitor PF-431396 (10), which shows off-target activity toward MLK3. We were able to develop highly active compounds in the single digit nanomolar range for MLK3. Furthermore, we achieved a dramatic shift in selectivity from FAK to MLK3. Here we present a new chemical class of MLK3 inhibitors, including our lead compound 37 with an outstanding IC50 value of <1 nM in a biochemical MLK3 assay while simultaneously exhibiting kinome-wide selectivity.
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000295900 7001_ $$00000-0002-1252-1829$$aSchwalm, Martin P$$b1
000295900 7001_ $$aKrämer, Andreas$$b2
000295900 7001_ $$aElson, Lewis$$b3
000295900 7001_ $$aRasch, Alexander$$b4
000295900 7001_ $$00000-0003-2041-4983$$aMasberg, Benedikt$$b5
000295900 7001_ $$00000-0002-5375-2156$$aSelig, Roland$$b6
000295900 7001_ $$aSievers-Engler, Adrian$$b7
000295900 7001_ $$00000-0002-1318-0974$$aLämmerhofer, Michael$$b8
000295900 7001_ $$00000-0003-2402-4157$$aMüller, Susanne$$b9
000295900 7001_ $$00000-0001-5995-6494$$aKnapp, Stefan$$b10
000295900 7001_ $$aAlbrecht, Wolfgang$$b11
000295900 7001_ $$00000-0001-6952-1486$$aLaufer, Stefan A$$b12
000295900 773__ $$0PERI:(DE-600)1491411-6$$a10.1021/acs.jmedchem.4c02552$$gp. acs.jmedchem.4c02552$$n1$$p674–694$$tJournal of medicinal chemistry$$v68$$x0095-9065$$y2025
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